Kataoka Yu, Hosoda Kiminori, Makino Hisashi, Matsubara Masaki, Matsuo Miki, Ohata Yoko, Koezuka Ryo, Tamanaha Tamiko, Tomita Tsutomu, Honda-Kohmo Kyoko, Noguchi Michio, Son Cheol, Nishimura Kunihiro, Asaumi Yasuhide, Miyamoto Yoshihiro, Noguchi Teruo, Yasuda Satoshi
Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Osaka, Japan.
Division of Atherosclerosis and Diabetes, National Cerebral & Cardiovascular Center, Osaka, Japan.
Cardiovasc Diagn Ther. 2019 Oct;9(5):431-438. doi: 10.21037/cdt.2019.09.02.
Patients with type 2 diabetes mellitus (T2DM) are high-risk subjects who more frequently have micro- and macrovascular diseases including coronary artery disease (CAD). Since impaired glycemic homeostasis directly influences the formation and propagation of atherosclerotic plaques, optimal management of glycemic status is required for the prevention of diabetic atherosclerosis. Continuous glucose monitoring (CGM) provides not only average glucose level but also the degree of glucose fluctuation and hypoglycemia. Given the association of glycemic variability with diabetic macrovascular diseases, CGM-based glycemic management could favorably modulate glycemic fluctuation, thereby potentially modifying atheroma burden in T2DM subjects. To test this hypothesis, the Observation of Coronary Atheroma Progression under Continuous Glucose Monitoring Guidance in Patients with Type 2 Diabetes Mellitus (OPTIMAL) study has been designed (Japan Registry of Clinical Trials: jRCT1052180152, University Hospital Medical Information Network Clinical Trial Registry UMIN000036721).
The OPTIMAL is a single-center, randomized trial to evaluate the efficacy of CGM-based glycemic control on atheroma progression in T2DM patients with CAD by using serial intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. A total of 90 eligible subjects will be randomized 1:1 into two groups to receive either CGM-based glycemic control or HbA1c-baded glycemic management. Coronary angiography and NIRS/IVUS imaging is repeated at the end of the assigned treatment period.
The primary endpoint is the normalized absolute change in total atheroma volume (TAV) from baseline to 12 months. The secondary endpoints include (I) the absolute change in percent atheroma volume, (II) the percent change in lipid core burden index, (III) the change in coefficient variance measured by CGM, (IV) the change in atherogenic markers (high-density lipoprotein functionality, proprotein convertase subxilisin/kexin type 9 and fatty-acid binding proteins), and (V) the frequency of hypoglycemia. Safety will also be evaluated.
The collaboration of CGM use with serial NIRS/IVUS imaging will enable to compare atheroma progression rate under CGM-based glycemic management and HbA1c-based approach.
2型糖尿病（T2DM）患者是高危人群，更易患微血管和大血管疾病，包括冠状动脉疾病（CAD）。由于血糖稳态受损直接影响动脉粥样硬化斑块的形成和发展，因此需要对血糖状态进行优化管理以预防糖尿病性动脉粥样硬化。连续血糖监测（CGM）不仅能提供平均血糖水平，还能反映血糖波动程度和低血糖情况。鉴于血糖变异性与糖尿病大血管疾病的关联，基于CGM的血糖管理可能会有利地调节血糖波动，从而有可能减轻T2DM患者的动脉粥样硬化负担。为验证这一假设，设计了2型糖尿病患者连续血糖监测指导下冠状动脉粥样硬化进展观察（OPTIMAL）研究（日本临床试验注册中心：jRCT1052180152，大学医院医学信息网络临床试验注册中心UMIN000036721）。
OPTIMAL是一项单中心随机试验，通过使用连续血管内超声（IVUS）和近红外光谱（NIRS）成像，评估基于CGM的血糖控制对CAD合并T2DM患者动脉粥样硬化进展的疗效。总共90名符合条件的受试者将按1:1随机分为两组，分别接受基于CGM的血糖控制或基于糖化血红蛋白（HbA1c）的血糖管理。在指定治疗期结束时重复进行冠状动脉造影和NIRS/IVUS成像。
主要终点是从基线到12个月总动脉粥样硬化体积（TAV）的标准化绝对变化。次要终点包括：（I）动脉粥样硬化体积百分比的绝对变化；（II）脂质核心负担指数的百分比变化；（III）通过CGM测量的变异系数变化；（IV）致动脉粥样硬化标志物（高密度脂蛋白功能、前蛋白转化酶枯草溶菌素/kexin 9型和脂肪酸结合蛋白）的变化；（V）低血糖发生频率。同时也将评估安全性。
CGM与连续NIRS/IVUS成像相结合，将能够比较基于CGM的血糖管理和基于HbA1c的方法下动脉粥样硬化的进展速度。
